Ghrelin modulates encoding-related brain function without enhancing memory formation in humans

Abstract

Ghrelin regulates energy homeostasis in various species and enhances memory in rodent models. In humans, the role of ghrelin in cognitive processes has yet to be characterized. Here we show in a double-blind randomized crossover design that acute administration of ghrelin alters encoding-related brain activity, however does not enhance memory formation in humans. Twenty-one healthy young male participants had to memorize food- and non-food-related words presented on a background of a virtual navigational route while undergoing fMRI recordings. After acute ghrelin administration, we observed decreased post-encoding resting state fMRI connectivity between the caudate nucleus and the insula, amygdala, and orbitofrontal cortex. In addition, brain activity related to subsequent memory performance was modulated by ghrelin. On the next day, however, no differences were found in free word recall or cued location-word association recall between conditions; and ghrelin's effects on brain activity or functional connectivity were unrelated to memory performance. Further, ghrelin had no effect on a cognitive test battery comprising tests for working memory, fluid reasoning, creativity, mental speed, and attention. In conclusion, in contrast to studies with animal models, we did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans.

Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism

“…Moreover, in animals, ghrelin regulates hippocampal spine synapse density and long-term potentiation and enhances spatial learning and memory [ 89 ]. However, Kunath et al [ 90 ] did not find any evidence for the potential of ghrelin acting as a short-term cognitive enhancer in humans. It has been found that viewing food pictures does not affect total calorie intake and ghrelin levels, but improves postprandial glucose levels [ 91 ].…”

Therapeutic Potential of Targeting the Ghrelin Pathway

“…However, the exact nature of the relationship between ghrelin and cognitive function in healthy subjects is still unclear, since plasma ghrelin levels have been reported to rather be inversely associated with cognitive function in elderly non-demented patients [181]. Additionally, a more recent study in healthy young subjects concluded that, in contrast to the animal data, acute ghrelin administration did not enhance any parameters of cognitive function, including memory, mental speed or attention [182]. …”

Interactions between metabolic, reward and cognitive processes in appetite control: Implications for novel weight management therapies

“…Consistent with this proposal, ghrelin administration to humans has been reported to enhance memory for food compared to non-food pictures in a simple recognition paradigm ( Malik et al, 2008 ) and increase hippocampal activation while viewing food pictures ( Goldstone et al, 2014 ). However, a recent study failed to identify an effect of ghrelin on either spatial memory encoding or consolidation ( Kunath et al, 2016 ) and there appears to be no clear relationship between cognitive function and serum ghrelin levels ( Gahete et al, 2011 ; Spitznagel et al, 2010 ; Stoyanova, 2014 ; Theodoropoulou et al, 2012 ). There is much still to learn about the potential cognitive enhancing effects of ghrelin in humans.…”